Biology subjects

Kleinjans, J.

Publications and source records attributed to Kleinjans, J..

3 recordsLinked to original sources

bioRxiv2022

Quantifying the number of translatable transcripts through the use of OMICs involved in post-transcriptional regulation.

Transcriptomics is nowadays frequently used as an analytical tool to study the extent of cell expression changes between two phenotypes or between different conditions. However, an important portion of the significant changes observed in transcriptomics at the gene level is usually not consistently detected at the protein level by proteomics. This poor correlation between the measured transcriptome and proteome is probably mainly due to post-transcriptional regulation, among which miRNA and circRNA have been proposed to play an important role. Therefore, since both miRNA and circRNA are also quantified by transcriptomics, we proposed to build a model taking those factors into account to estimate, for each transcript, the fraction of transcripts that would be available for translation. Using a dataset of cells exposed to diverse compounds, we evaluated how our model was able to improve the correlation between the assessed transcriptome and proteome expression level. The results show that the model improved the correlation for a subset of genes, probably due to the regulation of different miRNAs across the genome.

bioinformatics↗

bioRxiv2021

Contextualization of causal regulatory networks from toxicogenomics data applied to drug-induced liver injury

Toxicogenomics studies typically reveal a group of genes relevant to the pathophysiology of drug-induced organ injury. In recent years, network-based methods have become an attractive analytical approach as they can capture not only the global changes of regulatory gene networks but also the relationships between their components. Among them, a causal reasoning approach additionally depicts the mechanisms of regulation that connect upstream regulators in signaling networks towards their downstream gene targets. In this work, we applied CARNIVAL, a causal network contextualisation tool, to infer upstream regulatory signaling networks based on gene expression microarray data from the TG-GATEs database. We focussed on six compounds that induce observable histopathologies linked to drug-induced liver injury (DILI) from repeated dosing experiments in rats. We compared responses in vitro and in vivo to identify potential cross-platform concordances in rats as well as network preservations between rat and human. Our results showed similarities of enriched pathways and network motifs between compounds. These pathways and motifs induce the same pathology in rats but not in humans. In particular, the causal interactions "LCK activates SOCS3, which in turn inhibits TFDP1" was commonly identified as a regulatory path among the fibrosis-inducing compounds. This potential pathology-inducing regulation illustrates the value of our approach to generate hypotheses that can be further validated experimentally.

systems biology↗

bioRxiv2018

microRNA regulation of persistent stress-enhanced memory

Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stress disorder (PTSD) and related syndromes, which develop in a subset of individuals following a traumatic event. Using a stress-enhanced fear learning protocol that results in differential susceptibility in inbred mice, we integrated small-RNA sequencing with quantitative proteomics on basolateral amygdala tissue collected one month after training. We identified persistently changed microRNAs, including mir-135b-5p, and predicted target proteins associated with PTSD-like heightened fear expression. Functional manipulations of mir-135b-5p bidirectionally modulated stress-associated memory. mir-135b-5p is expressed in human amygdala and its passenger strand was elevated in serum from a well-characterized military PTSD cohort. miR-135b-5p is a therapeutic target for dampening persistent, stress-enhanced memory and its passenger strand a potential biomarker for responsivity to a mir-135-based therapeutic.\n\nOne Sentence Summarymir-135 can be manipulated to weaken persistent, stress-associated memory and serve as a biomarker of PTSD.

neuroscience↗